Preservation of fruits with sulfs 5-acetyl-8-hydroxy-quinoline preservation of fruits with sulate and dihydrogen phosphate salts of

ABSTRACT

A METHOD FOR PRESERVING EDIBLE FRUITS AND PARTS OF PLANTS AGAINST MICROBOIAL DETERIORATION BY MEANS OF MICROBICIDALLY EFFECTIVE AMOUNTS OF THE SULFATE AND PHOSPHATE SALTS OF 5-ACETYL-8-HYDROXY-QUINOLINE ARE DESCRIBED. WHILE 5-ACETYL-8-HYDROXY-QUINOLINE AND ITS HYDROCARCHLORIDE HAVE STRONG IRRITANT ACTION ON THE MUCOUS MEMBRANES AND SKIN OF HUMANS, THE NEW SALTS ARE VIRUTALLY FREE FROM THESE DRAWBACKS WHEN APPLIED IN MICROBICIDALLY EFFECTIVE AMOUNTS OF THE SURFACE OF EDIBLE PLANT PARTS.

United States Patent 3,759,719 PRESERVATION OF FRUITS WITH SULFATE ANDDIHYDROGEN PHOSPHATE SALTS OF S-ACETYL-S-HYDROXY-QUINOLINE Ernst Hodeland Karl Gatzi, Basel, Switzerland, assignors to Ciba-Geigy Corporation,Ardsley, N.Y.

No Drawing. Continuation-impart of abandoned application Ser. No.704,588, Feb. 12, 1968. This application Dec. 8, 1970, Ser. No. 96,240

Claims priority, application Switzerland, Feb. 16, 1967,

2,281/67 Int. Cl. A23b 7/00 US. Cl. 99-154 Claims ABSTRACT OF THEDISCLOSURE A method for preserving edible fruits and parts of plantsagainst microbial deterioration by means of microbicidally effectiveamounts of the sulfate and phosphate salts of 5aoetyl-8-hydroxy-quinoline are described. While5-acetyl-S-hydroxy-quinoline and its hydrochloride have strong irritantaction on the mucous membranes and skin of humans, the new salts arevirtually free from these drawbacks when applied in microbicidallyeifective amounts to the surface of edible plant parts.

This application is a continuation-in-part of our application Ser. No.704,588, filed Feb. 12, 1968, and now abandoned.

BACKGROUND OF THE INVENTION A series of mierobicidal active substancesfor conserving fruit is known from the literature, e.g. diphenyl, alkalimetal salts of o-hydroxydiphenyl, e.g. sodium-o-hydroxydiphenyl andsalicylanilide, also thiourea, ammonia, sulphur dioxide, carbon dioxideetc. [Ullmann, 3rd edition, vol. 11, pp. 440-462 (1960)]. Suchsubstances, however, olny partially meet the desired requirements aseither the breadth and duration of action is too slight or they are tootoxic to Warm blooded animals or they have an unpleasant smell.

DESCRIPTION OF PRIOR ART The base S-acetyl-8-hydroxy-quinoline itself aswell as its acid sulfate salt (5-acetyl-S-hydroxy-quinoline hydrogensulfate) ('JOCHa e OHIII M.P. 248 C. with decomposition are known fromJ. Am. Chem. Soc. 52, 4433-4436 (1930); the fungicidal activity of thebase is known from German Pat. No. 961,668 or the British Pat. 776,223.It is also known that S-acetyl-S-hydroxy-quinoline and its hydrochloridehave a strong irritant action on the skin and mucous membranes.

DETAILED DISCLOSURE The present invention concerns a method forpreserving fruits and other edible parts of plants using mierobicidal3,759,719 Patented Sept. 18, 1973 r OOCH:

SO-i

fea OH H J2 M.P. 237-233 C.

COCH;

03, Jamil M.P. 230-235 C. with decomposition furor These salts have notbeen known hitherto.

It has been found that these salts have excellent microbicidalproperties. They are active very particularly against a broad spectrumof microoganisms which attack fruits, roots or other edible parts ofplants after harvesting, among which microorganisms there are especiallybacteria, yeasts and fungi. The new salts are particularly valuable forthis reason as active substances in preserving agents which are used,e.g. for citrus fruits such as grapefruit, oranges, lemons, alsobananas, pineapple, avocados, mango, guajava, litchi, nut kernels,apples, pears, peaches, apricots, plums, grapes, strawberries, guava,sweet potatoes, potatoes, yams, carrots, turnips, sugar beet, onions,lettuce, artichokes, cabbage, asparagus, edible mushrooms, etc, Inaddition, these salts also have the other properties required of activesubstances for food preservatives, i.e. in the concentration necessaryto preserve foodstuffs they are non-toxic to man and they have noadverse elfect on the taste and smell of the foodstuff. These new saltsare practically neutral compounds and do not alter the pH of thesubstrate; furthermore they do not or to a much smaller extent irritatethe skin and mucous membranes of humans; also they are non-toxic to manunder the above-described conditions and are, therefore, particularlysuitable for practical uses as food preservatives.

The aforesaid new salts can be produced by conventional processes, e.g.by reaction of 5-acetyl-8-hydroxyquinoline with the equivalent amount ofacid. They are compounds which crystallise well, they are very stable inair and, in contrast to S-acetyl-S-hydroxy-quinoline itself, also inneutral or weakly acid media.

These two salts are distinguished by good fungicidal properties. Theyare soluble to a certain extent in water and in organic solvents.

As preserving agents these salts are applied in an amount of from about0.005 to about 2.0, preferably about 0.01 to about 0.5 milligram persquare centimeter of the surface of the fruit, plant or plant part to betreated.

The fungitoxic action of the new salts and of some substances known fromthe prior art was determined by the so-called spore germination test onthe following types of fungi:

Penicillium italicum Penicillium digitatum The test was run withhealthy, completely ripened oranges and for each run 20 fruits wereused. The orange peel was injured by means of a small board fitted withneedles, with which 30 pinpri'cks, about 2 mm. deep, were applied toeach orange. The fruits were then dipped during Rhizopus nigricans 5Aspergillus Niger one minute at room temperature into an aqueous suspen-Botrytis cinerea sion of spores of Penicillz'um' digitatum, contalnlngabout 100,000 spores per milliliter and left to dry. Then they 1 Of a05%, 01% and 0.01% solution of each were dipped for one minute intoanother aqueous solution active substance in a suitable solvent such asacetone 1s or suspension, also at room temperature, containing 1% byplaced on 2 glass slides (26 x 76 mm.) under the same weight of thesubstance to be tested. The fruits were then conditions. The solvent isevaporated off and a uniform left to dry and packed into two paper bagseach containing coating of active substance is obtained on the glassslides. 10 oran The bags w r to ed at oo temperature, The slides areinoculated with spores of the above fungi The evaluation of the fruitswas made the 5th and the 8th and then kept in dishes at room temperaturein an atmosday after treatment and the oranges were inspected foratphere which is almost saturated with steam. The germitack byPenicillium. digitatum. nated spores are counted twice, once after 48hours and A control run of oranges was injured and exposed to the secondtime after 72 hours. The results are summarlsed the suspension of sporesof Penicillium digitatum the same in the following tables. way but nottreated with active substance.

TABLE I Action against Penicillium Penicillium AspergilluaConeenitalz'cum digitatum niger tration, Compound percent 48 hr. 72 hr.48 hr. 72 hr. 48 hr. 72 hr.

5-acet l-B-hydroxy-qm'noline dihydrogen phosphate 0.1 y 0. or

Bis-(5-acetyl-S-hydroxy-quinoline) sulfate 00b} +i i h 1- 0.1 D p my0.01

S d hloro hen l henolate 0.1 o lum-o-c P y P am Tetra-methyl thiuremdi-sulfide 0. 1 0. 01

Control TABLE H The results are shown in Table III.

Concen- Botrytis cinerea TABLE III tration, Compound percent 48 72 hrEvaluation of oranges Bis-(5-aeetyl-8-hydroxy-quinoline) sulfate 0.1ways sdays 01 After infection by Penicillium digitat'um Diphenyl ISubstance to be tested Infected Healthy Infected Healthy Tetramethylthiuram di-sulfide 0 I sulfate 1 19 10 10 I 5-acetyl-8-hydroxy- Controlguinoline (base) 9 11 14 6 LEGEND: ++=Complete inhibition of germinationcaused by residue figg i fi oil ccm. of solution of active substance.+=A to 90% inhibition of (ohinosol) 2 18 20 0 germination caused byresidue of 1 cem. of solution of active substance, None (control') 9 1120 0 -=No inhibition of germination. 5

Fruit and other edible parts of plants are preserved new Salts y 0 PPdlrecfly as an aqueous according to the invention by providing them witha pro- Q P Preferably in the form of a ready made pfi coating of h newSalts b i h di i spraying, plication form. Such a paste, a pulverulantconcentrate, an washing or Painting h i liquid or Waxy preparaemulsionconcentrate and a wax are described below; tions containing amicrobicidally effective amount of the 0 Where not expressly Stated,PartS aI1d p are y active substances. In many cases, because of theiradvan- Wflght- Temperatures are given 111 degrees Celltlgfadetageoussolubility in water, the new microbicidal salts Paste can be used in theform of aqueous solutions. On the other hand, it is possible to mix theactive substances 20 parts of bis(s'acetyl's'hydroxy'qumohne) Sulfatetogether with Suitable nondnjurimls dispersing agents 20 parts of a 1%aqueous hydroxyethyl cellulose solution such as vegetable oils, fats orwaxes and to use these dispersible preparations as aqueous or anhydrousdispersions.

Solvents suitable for use in such dispersions are non- 3 parts ofditertiary acetylene glycol 57 parts of distilled water are milled andhomogenised in a mixer into a thinly flowing 20% paste. On directaddition to water, the paste toxic, low-boiling, organic solvents suchas low-molecular forms a milky dispersion. Freshly harvested oranges arehydrocarbons, such as pentane, hexane, ketones, alcohols and ethers,such as methoxy ethanol or ethoxy ethanol.

A test to preserve oranges was made wtih the bis-(5-acetyl-S-hydroxy-quinoline) sulfate and two substances known from theprior art.

dipped into a 1% dispersion and allowed to drip dry. About 0.01 to 0.1mg. of active substance remained on the fruit per crn. surface. It wasobserved that the fruit showed no damage whatever due to micro-organismsafter several days.

Pulverulent concentrate 95 parts of bis-(S-acetyl-8-hydroxy-quinoline)sulfate and parts of a condensation product of nonylphenol and ethyleneoxide (molar ratio 1:9 to 1:10) or another suitable, preferablynon-ionic, wetting agent are homogenised and finely milled in a suitablemill. This pulverulant concentrate is not dusty and quickly dissolves inwater. A suspension, in 1% concentration, evenly wets fruit treatedtherewith.

Emulsion concentrate parts of S-acetyl-S-hydroxy-quinolinedihydrogen-phosphate parts of ethoxyethanol 15 parts of dimethylformamide 10 parts of emulsifying agent consisting of a mixture ofcalcium dodecylbenzene sulphonate and the condensation product ofnonylphenol and ethylene oxide (molar ratio about 1:8 to 1:10)

50 parts of petroleum (boiling range 230-270).

This mixture is a 10% emulsion concentrate which can be diluted withwater to form emulsions of any concentration desired.

A 1% aqueous emulsion is used for the treatment of mould (e.g.Penicillium italicum) on grapefruit. For this purpose, the fruit isdipped in the emulsion and left there for a few seconds. It is thenallowed .to drip dry. About 0.01 to 0.1 mg. of active substance remainson the fruit per cm. surface. The emulsion can also be sprayed on to thegrapefruit or the latter can be washed therewith or can be appliedthereto with a brush. The attack by fungi is greatly reduced by thistreatment and any new infection is prevented.

Parafiin blocks 890 parts of melted soft paraffin (M.P. 41-43) are mixedwith 100 parts of parafiin oil at about 60, and 10 parts of very finelyground (average particle size -50 microns)bis-(S-acetyl-8-hydroxyquinoline) sulfate are worked in until ahomogeneous substance is obtained, which is poured into forms and thenallowed to harden.

The resulting blocks are then used in a molten state in suitableapparatus, with slight heating, to coat citrus fruit with a thin film ofbis-(5-acetyl-8-hydroxyquinoline) sulfate in paraffin and thus protectthem against spoilage. This apparatus may wax the surface of the citrusfruit e.g. by a rubbing action.

The consistency of the blocks can be varied as desired by increasing theamount of paraffin oil and also optionally adding surfactants such assorbitan fatty acid esters, e.g. sorbitan-sesquioleate,sorbitan-monooleate, sorbitan-trioleate, polyoxyethylene-sorbitan fattyacid esters, to obtain an increasingly softer block, thus adjusting theconsistency to the requirements of the particular coating apparatus'used.

Paraflin emulsion 440 parts of soft paraffin (M.P. 41-43), 220 parts ofparaflin oil, and 50 parts of Arlacel 83 (sorbitan-sesquioleate) aremelted together while stirring at 5060". A hot solution (80") of 300parts of distilled water and 10 parts ofbis-(5-aceto-8-hydroxyquinoline) sulfate is stirred into the melt whichis still warm (50) with a suitable stirring apparatus (e.g. aHomorex-mixer) until a homogeneous substance is obtained.

The resulting water-in-oil emulsion is stirred while allowing to cool toabout 30". A creamy substance of soft consistency is obtained, which canbe applied in suitable apparatus, e.g. by brushing, or lightly rubbingthe peel of citrus fruit.

The concentration of active substance in the composition can also bevaried (e.g. 0.5% or 1.5%). In lieu of Arlacel 83, other paraffinemulsifying agents, e.g. mixtures of Span and (sorbitan-monooleate andsorbitan-trioleate) can be used as well as other inert substancessuitable for preparing similar water-in-oil emulsions of end productshaving optimal consistency, whereby the consistency can be adapted tothe requirements of the particular apparatus used for wax-coating thecitrus fruit.

The term edible parts of plants as used in this specification and theappended claims refers to edible blossoms,

seeds, fruit, leaves, sprouts, roots, bulbs and/or tubers of plants.

We claim:

1. A method for protecting fruits and edible parts of plants againstmicrobial deterioration, comprising applying to the surface of suchplant part a microbicidally effective amount of a preserving agentselected from the bis-(5- acetyl-8-hydroxyquinoline) sulfate, M.P.237-238 C., the 5-acetyl-8-hydroxyquinoline dihydrogen phosphate, M.P.230-235 C. and a mixture thereof.

2. A method as described in claim 1, wherein said salt or mixture ofsalts is applied, per square centimeter of said plant part surface, inan amount of at least 0.01 milligram.

3. A method as described in claim 1, wherein said salt or mixture ofsalts is applied, per square centimeter of said plant part surface, inan amount of from 0.01 to about 0.5 milligram.

4. A method as described in claim 1, wherein said salt i2s3sbis5-acetyl-8-hydroxyquinoline) sulfate, M.P. 237- 5. A method asdescribed in claim 1, wherein said salt is S-acetyl-8-hydroxyquinolinedihydrogen phosphate, M.P. 230-235 C.

References Cited UNITED STATES PATENTS 2,606,189 8/1952 Grier 260-2862,615,814 11/1952 Geary 99-154 FOREIGN PATENTS 776,223 6/1955 England.

OTHER REFERENCES Chem. Abstracts, vol. 55, 11552, 1961, QuinolinDerivatives as Anti-Infective Agents, Bahal.

NORMAN YUDKOFF, Primary Examiner H. H. BERNSTEIN, Assistant ExaminerU.S. Cl. X.R. 260-286; 99-103

